Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands; 2 Comprehensive Heart Failure Center, University of
Wrzburg, Wrzburg, Germany; and 3 Department of Internal MedicineCardiology, University Hospital Wrzburg, Germany
Coincidence of COPD and heart failure (HF) is challenging as both diseases interact on multiple levels with each other, and thus impact
significantly on diagnosis, disease severity classification, and choice of medical therapy. The current overview aims to educate caregivers
involved in the daily management of patients with HF and (possibly) concurrent COPD in how to deal with clinically relevant issues such as
interpreting spirometry, the potential role of extensive pulmonary function testing, and finally, the potential beneficial, but also detrimental
effects of medication used for HF and COPD on either disease.
..........................................................................................................
Heart failure
COPD misdiagnosis
Severity classification
Introduction
A 60 year old man (110 kg, 170 cm) consults his general practitioner (GP) because of progressive dyspnoea on minimal exertion.
The patient is an active smoker (40 pack-years) with a history
of diabetes type 2, obesity, hyperlipidaemia, and hypertension. He
reported a weight gain of 4 kg within the last 3 days. At clinical
examination the GP detects increased jugular venous pressure, pulmonary expiratory wheezing, a broadened and sustained apex beat
in the lateral decubitus position, ankle oedema, and a high systolic
blood pressure of 180 mmHg. The forced expiratory volume in
1 s/forced vital capacity ratio (FEV1 /FVC) measured by a hand-held
spirometer is 0.60 post-bronchodilator and thus would be compatible with pulmonary obstruction as seen in COPD. The reversibility
of the FEV1 value, 15 min after salbutamol inhalation, lies in the grey
zone, i.e. 9%.
This scenario describes a common dilemma in everyday clinical
practice. Does this patient have COPD, heart failure (HF), or both?
In order to arrive at an accurate diagnosis, the recent guidelines
on HF and COPD both emphasize not to rely on the assessment
...........................................................
Keywords
*Corresponding author. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85060, Stratenum 6.131, 3508 AB Utrecht, The
Netherlands. Tel: +31 88 7568193, Fax: +31 88 7569028, E-mail: F.H.Rutten@umcutrecht.nl
........................................................................................................................................................................
G. Gder et al.
HF
phenotype
Time point
of measurements
Iversen, 200814
532
Mixed
13 days after
hospitalization for
acute HF
Mascarenhas, 200822
223
309
186
Apostolovic, 201113
Macchia, 201120
Boschetto, 201224
Steinacher, 201226
89
Brenner, 20134
272
619
Begh, 201325
124
HFeEF
Minasian, 201323
187
Minasian, 201321
116
Stable, outpatients
department
35 days after
hospitalization for
acute HF
Stable, outpatients
department
Stable, outpatients
department
Stable, outpatients
department
Stable, outpatients
department
Prevalence Prevalence of
of COPDa never-smokers
in patients
with COPD
35%b
41%b
31%b
39%
27.6%
37%
30%
44%
20%
29% (no)
No specification, 49% in
the total cohort
54%
87% (no)
No specification for
GOLD-COPD
0%, >10 pack-years of
smoking was an
inclusion criterion
No specification for
GOLD-COPD
Not mentioned
19%
100% no)
83% (no)
98% (no)
92% (no)
28%
91% (no)
83% (no)
32
34
6%
34%
.........................................
FEV1 , forced expiratory volume in 1 s; FVC, forced vital capacity; HF, heart failure; HFpEF heart failure with preserved ejection fraction; HFrEF, heart failure with reduced
ejection fraction.
a COPD prevalence in patients with HF according to the GOLD definition (post-bronchdilator FEV /FVC ratio <0.7).
1
b Exclusion of GOLD stage I patients (FEV >80% of predicted).
1
........................................................................................................................................................................
G. Gder et al.
Severity
Post-bronchodilator
FEV1 % of predicted level
................................................................
GOLD 1
GOLD 2
GOLD 3
GOLD 4
Mild
Moderate
Severe
Very severe
80%
50 to <80%
30 to <50%
<30 %
D
D
Alternative choices:
Short-acting anticholinergic
OR
Short-acting beta2-agonist
A
A
Long-acting anticholinergic
OR
Long-acting beta2-agonist
Alternative choices:
Alternative choice:
Long-acting anticholinergic
Long-acting beta2-agonist
Short-acting anticholinergic + short-acting beta2-agonist
mMRC < 2
CAT < 10
2/year
Alternative choices:
FEV1 50%
C
C
B
B
Exacerbation frequency
< 2/year
Spirometry
mMRC 2
CAT 10
Figure 1 Proposed grading scheme: patients are allocated to groups AD according to the forced expiratory volume in 1 s (FEV1 ) % of
..............................................................
predicted level, the number of COPD exacerbations within the last 12 months, and symptoms. Symptoms are assessed using either the
Modified Medical Research Council Dyspnea Scale (mMRC) or the COPD Assessment Test (CAT). The mMRC contains five categories that
describe incremental symptom severity (0 = breathlessness only at strenuous exercise, 1 = dyspnoea when hurrying on level ground or
walking up a slight hill, 2 = walking more slowly than people of the same age because of dyspnoea on level ground, 3 = dyspnoea after walking
100 yards or after a few minutes on level ground. 4 = dyspnoea when dressing). The CAT assesses eight questions on typical symptoms of
daily life with COPD. Each question is rated from 0 to 5 points according to severity of symptoms. Questions refer to coughing frequency,
phlegm production, angina pectoris, dyspnoea uphill, limitations at daily activities, functionally fixed to domestic environment due to dypsnoea,
sleep disturbances, and physical energy. Adapted from Vestbo et al.1
G. Gder et al.
Table 3 Effects of beta-blockers on resting spirometry in patients with heart failure only, and in patients with heart
failure and chronic obstructive pulmonary disease
Study design, n,
HF
Studied
Effects on
First author,
study duration
phenotype
beta-blocker
spirometry
year,
refence no.
...........................................................................................................................................
HF
Agostoni, 200240 RCT double blind, crossover HFrEF <40%, COPD
Carvedilol vs. placebo
Difference between carvedilol and
study, n = 15, 4 months
excluded
placebo: no effects on FEV1 , VC,
DLCO
beta-blocker use
Cohort study, n = 35 with
HFrEF <40%, COPD
Carvedilol (n =11),
Difference between baseline and
Witte, 200541
PFT on 12 months
excluded
bisoprolol (n = 24)
follow-up (n = 35): FEV1 , 84%
(19)% to 79 (21)% (P <0.01); FVC.
follow-up
no effects. No difference between
both beta-blockers
Agostoni, 200742 RCT, double blind crossover HF with NYHA II or LVEF Carvedilol vs. isoprolol
Difference between carvedilol and
study, n = 53, 2 months
<45%; severe COPD
bisoprolol: FEV1 (L): 2.71 vs.
2.83 L (P = 0.03); VC, no effects.
excluded
Analyses refer to
post-bronchodilator values
Difference between carvedilol and
Dungen, 201143 RCT, open label, n = 714 with HF with NYHA II or LVEF Carvedilol (n = 365) vs.
PFT, 12 weeks
<45%
bisoprolol (n = 349)
bisoprolol: FEV1 . +50 mL
(P = 0.03) for bisoprolol; FVC, not
reported
HF + COPD
HFrEF <40% and COPD
Bisoprolol (n = 14) vs
Difference between bisoprolol and
Hawkins, 200945 RCT, placebo controlled,
n = 27, 4 months
GOLD 2, 3
placebo (n = 13)
placebo: FEV1 , 70 vs. 120 mL
(P<0.05); FEV1
post-salbutamol, 90 vs. 20 mL
(P<0.05). No change on VC, RV,
TLC, PEF
Jabbour, 201146 RCT, open label, triple
HF (mean LVEF 37%), COPD Carvedilol, bisoprolol and
Difference for FVC: no effects in all
crossover study, n = 51,
GOLD 2, 3, 16 HF only 35
metoprolol succinate
subgroups. Difference between
each 6 weeks
CHF + COPD
bisoprolol vs. carvedilol, CHF,
FEV1 , +120 ml for bisoprolol
(P = 0.02); CHF + COPD, FEV1 ,
+150 mL for bisoprolol (P = 0.01)
Difference between metoprolol
vs. carvedilol: total group, FEV1 , +
80 mL for metoprolol (P = 0.04)
Bisoprolol vs. metoprolol: no
difference
Carvedilol (n = 31) vs.
Change in FEV1 between baseline
Lainscak, 201147 RCT, open label, n = 63, 46 HFrEF (LVEF <40%) and
weeks after up-titration
COPD GOLD 2
bisoprolol (n = 32)
and follow-up: bisoprolol, 1561 to
1698 mL (P = 0.046); carvedilol,
1704 to 1734 mL (P = 0.44). No
between-group difference for
FEV1 FVC: no effects
In patients with HF and COPD, beta-blocker-induced reduction of FEV1 might be even stronger. In an RCT conducted
by Hawkins et al., FEV1 was reduced between baseline and 4
months of follow-up with bisoprolol (70 mL) but not with placebo
(+120 mL).45 Another RCT that compared carvedilol with bisoprolol could show an increase of FEV1 by 137 mL for bisoprolol after
................
All studies were performed in patients with HF when in a stable phase of their disease.
CHF, congestive heart failure; DLCO, diffusing capacity of the lung for carbon monoxide; FEV1 , forced expiratory volume in 1 s; FVC, forced vital capacity; HF, heart failure;
HFrEF, heart failure with reduced ejection fraction; PEF, peak expiratory flow; PFT, pulmonary function test; RCT, randomized controlled trial; TLC, total lung capacity; VC,
vital capscity.
........................................................................................................................................................................
Conclusions
In patients with HF, a (post-dilatory) FEV1 /FVC ratio <0.7 is insufficient to diagnose true COPD. Because of the potential risk of detrimental effects of bronchodilators in cardiac patients, and in order
to prevent unnecessary polypharmacy, long-acting bronchodilators
should only be started or maintained in subjects with true COPD.
Inhalative therapy should be preferred over oral, as systemic effects
........................................................................................................................................................................................................................
were related to severe side effects especially in patients with underlying cardiovascular diseases.
In any case, after initiation of bronchodilators, physicians should
carefully monitor symptom improvements and side effects in
patients with HF, and eventually consider drug discontinuation.
G. Gder et al.
Funding
G.G. was supported by a fellowship grant from the Medical Faculty of the University of Wrzburg (Habilitationsstipendium). This
work was supported by grants from the German Ministry of Education and Research (BMBF), Berlin, Germany [BMBF 01EO1004;
Comprehensive Heart Failure Center Wrzburg].
Conflict of interest: none declared.
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